The risk for developing a substance abuse (SA) disorder is not randomly or equally distributed in the population. Certain individuals are especially susceptible or vulnerable to SA. However, the biological mechanisms and overt characteristics concomitant to SA vulnerability are not known. Identifying and delineating the basis of SA vulnerability would greatly improve the efficacy of both rehabilitation and prevention interventions; in effect such information would enable deriving empirically sound treatment procedures that are targeted to the particular predisposing disturbance or deviation. Children of substance abusers are at high risk for developing a SA disorder. Thus, an economical and pragmatic research strategy for elucidating the determinants of SA risk is to investigate comprehensively the offspring of substance abusers. Employing this method of risk ascertainment, the proposed Center has five broadbased objectives: 1) delineate the biobehavioral characteristics associated with SA vulnerability; 2) empirically derive subtypes of SA vulnerability; 3) conduct a prospective longitudinal investigation of high and low risk children; 4) cross-validate the characteristics and subtypes of SA vulnerability in a sample of current adolescent substance abusers; and, 5) ascertain the specificity of SA vulnerability with respect to the most common comorbid feature of SA, namely, a conduct disorder. In order to meet these objectives, the multidisciplinary Center faculty are grouped into four investigative modules and two support modules. Each investigative research module will address vulnerability to substance abuse disorders according to a different level of biological organization. The support modules deal with data management, statistical analysis, education and training. All of the data obtained from individual components will be integrated, and accessible to all Center investigators, thereby promoting collaboration and new heuristic lines of research.